- EDITION III, IV and JP I studies meet primary endpoint -

PARIS, Dec. 3, 2013 /PRNewswire/ -- Sanofi announced the full results from the EDITION II study showing that investigational new insulin U300 demonstrated similar blood sugar control with 23% fewer patients experiencing night-time low blood sugar compared with Lantus® (insulin glargine [rDNA origin] injection). These results were presented today at the International Diabetes Federation 2013 World Diabetes Congress in Melbourne, Australia. The full EDITION II results are consistent with those from EDITION I.1 Both studies were conducted in people with type 2 diabetes already using basal insulin (with mealtime insulin or oral medication).

Sanofi also announced today additional topline results from the EDITION Phase 3 clinical program. The primary endpoint was met in the 6-month EDITION III, EDITION IV and EDITION JP I studies. Full results will be presented at scientific meetings in 2014.

"We are encouraged by these results which suggest that U300 could be a viable treatment option for a wide range of people with type 1 and type 2 diabetes," commented Pierre Chancel, Senior Vice President, Global Diabetes, Sanofi.

EDITION II Full ResultsEDITION II included type 2 diabetes patients, who failed to control their blood sugar levels on previous basal insulin and oral medication, together with a long duration of disease and high body mass index (BMI). The study randomized 811 participants (1:1) to U300 (n=404) or Lantus® (n=407) once daily in the evening, while continuing oral anti-diabetics.

The percentage of participants with severe or confirmed (defined by plasma glucose less than or equal to 70 mg/dL) night-time low blood sugar levels (nocturnal hypoglycemia) from month 3 to 6 was significantly lower with U300 vs. Lantus® [21.6% vs. 27.9%; relative risk (RR) 0.77 (95% CI: 0.61 to 0.99); p=0.038]. Over the 6-month treatment period, the incidence of any nocturnal hypoglycemia (% of participants with greater than or equal to 1 event) was lower with U300 vs. Lantus® [30.5% vs. 41.6%; RR 0.73 (95% CI: 0.60 to 0.89)] as was the incidence of any hypoglycemic event at any time of the day (over a 24 hour period) [U300: 71.5%; Lantus®: 79.3%; RR 0.90 (95% CI: 0.84 to 0.97)]. This result was also obtained across the entire 6-month study period, including the first 8 weeks of the trial.

There were similar findings between groups for adverse events, including injection site reactions and hypersensitivity reactions.

"Reducing the risk of hypoglycemic events is imperative for effective management of diabetes, and EDITION II suggests that U300 reduces the risk of these events, even in a challenging patient population who have been on high basal insulin doses and oral medications without being able to achieve their treatment targets," said Hannele Yki-Jarvinen, Professor of Medicine, University of Helsinki, Finland.

EDITION III topline results (study in insulin-naive people with type 2 diabetes)EDITION III compared U300 with Lantus® in 878 people with type 2 diabetes not previously treated with insulin and uncontrolled on oral medication. The primary endpoint of similar blood sugar level control (measured by HbA1c) from baseline to month 6 was met (-1.42% [95% CI: -1.511 to -1.326] in the U300 group, and -1.46% [95% CI: -1.555 to -1.367] in the Lantus® group).

Consistent with the results of the EDITION I and II studies, the rates of severe or nocturnal confirmed hypoglycemia in EDITION III from month 3 to 6 (main secondary endpoint) were lower with U300 (15.5% for U300 vs. 17.4% for Lantus®), but unlike EDITION I and II, the reduction was not statistically significant. Overall incidence of any documented hypoglycemia during the entire 6-month treatment period was numerically lower in the U300 group than in the Lantus® group (49.9% vs. 55.3%; no statistical analysis was performed.)

EDITION IV and EDITION JP I topline results (studies in people with type 1 diabetes)EDITION IV and JP1 studies compared U300 with Lantus® in people with type 1 diabetes treated with basal and mealtime insulin. EDITION IV enrolled 549 patients internationally, while EDITION JP I was conducted in 243 Japanese patients. The primary endpoint was met in both studies which showed similar reductions in HbA1c from baseline between U300 and Lantus® at 6 months. (EDITION IV: -0.40% [95% CI: -0.501 to -0.299] in the U300 group, and -0.44% [95% CI: -0.543 to -0.344] in the Lantus® group); EDITION JP I: -0.30% [95% CI: -0.411 to -0.183] in the U300 group, and -0.43% [95% CI: -0.542 to -0.313] in the Lantus® group).

In EDITION IV and EDITION JP I, confirmed and severe nocturnal hypoglycemia from month 3 to 6 was not pre-specified as a main secondary endpoint per study protocol. Analyses of several hypoglycemia categories are underway and will be presented, together with the EDITION III full results, at medical congresses in the first half of 2014.

In all of the studies, no differences in other adverse events were observed between U300 and Lantus®.

Sanofi anticipates the regulatory submissions to U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the first half of 2014.

About the EDITION Phase 3 programThe EDITION program is a worldwide and comprehensive series of Phase 3 studies evaluating the efficacy and safety of new insulin U300 in broader and diverse populations of people with diabetes. The full EDITION I (basal insulin + mealtime insulin) results have already been released.1 The full EDITION II (basal insulin + oral therapy) results were presented at WDC 2013. Full results from EDITION III, EDITION IV, EDITION JP I, and EDITION JP II (Japanese type 2 diabetes patients treated with basal insulin + oral therapy) will be presented at scientific meetings in 2014.

About investigational new insulin U300Investigational new insulin U300 is a new formulation based on the glargine molecule, the biological entity of Lantus®, with its well established efficacy and safety profile. U300 has unique pharmacokinetic and pharmacodynamic profiles with studies demonstrating it has even flatter and more prolonged profiles than Lantus®.2-5 U300 also offers the benefit of a smaller volume of subcutaneous injection compared with Lantus®.

About Lantus (insulin glargine [rDNA origin] injection) Prescription Lantus is a long-acting insulin used to treat adults with type 2 diabetes and adults and patients (6 years and older) with type 1 diabetes for the control of high blood sugar. It should be taken once a day at the same time each day to lower blood glucose.

Do not use Lantus to treat diabetic ketoacidosis.

Important Safety Information for Lantus Do not take Lantus if you are allergic to insulin or any of the inactive ingredients in Lantus.

You must test your blood sugar levels while using insulin, such as Lantus. Do not make any changes to your dose or type of insulin without talking to your healthcare provider. Any change of insulin should be made cautiously and only under medical supervision.

Do NOT dilute or mix Lantus with any other insulin or solution. It will not work as intended and you may lose blood sugar control, which could be serious. Lantus must only be used if the solution is clear and colorless with no particles visible. Do not share needles, insulin pens or syringes with others.

Tell your doctor about other medicines, especially ones called TZDs (thiazolidinediones), and supplements you are taking because they can change the way insulin works. Before starting Lantus, tell your doctor about all your medical conditions including if you have heart failure or other heart problems, liver or kidney problems, are pregnant or planning to become pregnant, or are breast-feeding or planning to breast-feed. If you have heart failure, it may get worse while you take TZDs with Lantus.

The most common side effect of insulin, including Lantus, is low blood sugar (hypoglycemia), which may be serious. Some people may experience symptoms such as shaking, sweating, fast heartbeat, and blurred vision. Severe hypoglycemia may be serious and life threatening. It may cause harm to your heart or brain. Other possible side effects may include swelling, weight gain, injection site reactions, including changes in fat tissue at the injection site, and allergic reactions, including itching and rash. In rare cases, some allergic reactions may be life threatening.

About SanofiSanofi, an integrated global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients' needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

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